• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular basis of spinal glia/endothelium/neurons interaction as the mechanisms of development and maintenance of chronic pain

Research Project

Project/Area Number 25290016
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionHyogo Medical University

Principal Investigator

Noguchi Koichi  兵庫医科大学, 医学部, 教授 (10212127)

Co-Investigator(Renkei-kenkyūsha) YAGI Hideshi  兵庫医科大学, 医学部, 教授 (10303372)
YAMANAKA Hiroki  兵庫医科大学, 医学部, 講師 (20340995)
KOBAYASHI Kimiko  兵庫医科大学, 医学部, 講師 (70418961)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2013: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords神経障害性疼痛 / グリア / 脂質メディエーター / ニューロン / マイクログリア / プロスタグランジン / 合成酵素 / Rho / ROCK / p38
Outline of Final Research Achievements

Using rat neuropathic pain models, we found the following findings.
1. PGD2 produced by microglia is COX-1 dependent, and neurons in the spinal cord can receive PGD2 from microglia following peripheral nerve injury, suggesting a role of PGD2 signaling in mechanical allodynia. 2. We found the details of RhoA/ROCK pathway in spinal microglia in this model. It mediates p38 MAPK activation and morphological changes downstream of P2Y12/13 receptors in spinal microglia in neuropathic pain. 3. We found that increased artemin in peripheral tissues plays an important role on the regulation of TRPV1/A1 in DRG neurons in pathological conditions such as inflammatory and neuropathic pain. 4. Using electrophysiological method, we found leukotriene enhances NMDA-induced inward currents in dorsal horn neurons of the rat spinal cord after peripheral nerve injury. 5. We found that microglial TNF alpha is able to induce COX2 and PGI2 synthase expression in spinal endothelial cells during neuropathic pain.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (32 results)

All 2016 2015 2014 2013

All Journal Article (16 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 16 results,  Open Access: 5 results,  Acknowledgement Compliant: 6 results) Presentation (16 results) (of which Invited: 8 results)

  • [Journal Article] Macrophage-Colony Stimulating Factor Derived from Injured Primary Afferent Induces Proliferation of Spinal Microglia and Neuropathic Pain in Rats2016

    • Author(s)
      Masamichi Okubo, Hiroki Yamanaka, Kimiko Kobayashi, Yi Dai, Hirosato Kanda, Hideshi Yagi and Koichi Noguchi
    • Journal Title

      Plos ONE

      Volume: 11 Issue: 4 Pages: e0153375-e0153375

    • DOI

      10.1371/journal.pone.0153375

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Correlation Between DNA Methylation of TRPA1 and Chronic Pain States in Human Whole Blood Cells2016

    • Author(s)
      Sukenaga N, Ikeda-Miyagawa Y, Tanada D, Tunetoh T, Nakano S, Inui T, Satoh K, Okutani H, Noguchi K, Hirose M
    • Journal Title

      Pain Med

      Volume: in press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Annexin A2 in primary afferents contributes to neuropathic pain associated with tissue type plasminogen activator.2016

    • Author(s)
      Yamanaka H, Kobayashi K, Okubo M, Noguchi K.
    • Journal Title

      Neuroscience

      Volume: 314 Pages: 189-199

    • DOI

      10.1016/j.neuroscience.2015.11.058

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Elevated H2 O2 levels in TNBS-induced colitis rats contributes to visceral hyperalgesia through interaction with the TRPA1 cation channel.2016

    • Author(s)
      Kogure Y, Wang S, Tanaka KI, Hao Y, Yamamoto S, Nishiyama N, Noguchi K, Dai Y.
    • Journal Title

      J Gastroenterol Hepatol

      Volume: 未定 Issue: 6 Pages: 1147-1153

    • DOI

      10.1111/jgh.13226

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels.2016

    • Author(s)
      Iwaoka E, Wang S, Matsuyoshi N, Kogure Y, Aoki S, Yamamoto S, Noguchi K, Dai Y.
    • Journal Title

      J Nat Med

      Volume: 70 Issue: 1 Pages: 1-7

    • DOI

      10.1007/s11418-015-0929-1

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Leukotriene enhances NMDA-induced inward currents in dorsal horn neurons of the rat spinal cord after peripheral nerve injury2015

    • Author(s)
      Kiyoyuki Y, Taniguchi W, Okubo M, Yamanaka H, Kobayashi K, Nishio N, Nakatsuka T, Noguchi K
    • Journal Title

      Mol. Pain

      Volume: 11 Pages: 53-53

    • DOI

      10.1186/s12990-015-0059-5

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peripherally increased artemin is a key regulator of TRPA1/V1 expression in primary afferent neurons.2015

    • Author(s)
      Yasuko Ikeda-Miyagawa, Kimiko Kobayashi, Hiroki Yamanaka, Masamichi Okubo, Shenglan Wang, Yi Dai, Hideshi Yagi, Munetaka Hirose, Koichi Noguchi
    • Journal Title

      Mol Pain

      Volume: 11 Pages: 8-8

    • DOI

      10.1186/s12990-015-0004-7

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] De novo expression of Nav1.7 in injured putative proprioceptive afferents: Multiple tetrodotoxin sensitive sodium channels are retained in the dorsal root after spinal nerve ligation.2015

    • Author(s)
      Tetsuo Fukuoka, Kan Miyoshi, Koichi Noguchi
    • Journal Title

      Neuroscience

      Volume: 284 Pages: 693-706

    • DOI

      10.1016/j.neuroscience.2014.10.027

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] RhoA/ROCK pathway mediates p38 MAPK activation and morphological changes downstream of P2Y12/13 receptors in spinal microglia in neuropathic pain.2015

    • Author(s)
      Tatsumi E1, Yamanaka H, Kobayashi K, Yagi H, Sakagami M, Noguchi K.
    • Journal Title

      Glia

      Volume: 63 Issue: 2 Pages: 216-228

    • DOI

      10.1002/glia.22745

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Filamin A-interacting protein (FILIP) is a region-specific modulator of myosin 2b and controls spine morphology and NMDA receptor accumulation.2014

    • Author(s)
      Hideshi Yagi,Takashi Nagano,Min-Jue Xie,Hiroshi Ikeda,Kazuki Kuroda,Munekazu Komada,Tokuichi Iguchi,Rahman M. Tariqur,Soichi Morikubo,Koichi Noguchi,Kazuyuki Murase,Masaru Okabe& Makoto Sato
    • Journal Title

      Scientific reports

      Volume: 4 Issue: 1 Pages: 6353-6353

    • DOI

      10.1038/srep06353

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Xilei san ameliorates experimental colitis in rats by selectively degrading proinflammatory mediators and promoting mucosal repair.2014

    • Author(s)
      Hao Y, Nagase K, Hori K, Wang S, Kogure Y, Fukunaga K, Kashiwamura S, Yamamoto S, Nakamura S, Li J, Miwa H, Noguchi K, Dai Y.
    • Journal Title

      Evid Based Complement Alternat Med

      Volume: 2014 Issue: 1 Pages: 569587-569587

    • DOI

      10.1155/2014/569587

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Etodolac activates and desensitizes transient receptor potential ankyrin 12013

    • Author(s)
      Wang S, Dai Y, Kogure Y, Yamamoto S, Zhang W, Noguchi K
    • Journal Title

      J Neurosci Res

      Volume: 91(12) Issue: 12 Pages: 1591-8

    • DOI

      10.1002/jnr.23274

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Upregulated glial cell line-derived neurotrophic factor through cyclooxygenase-2 activation in the muscle is required for mechanical hyperalgesia after exercise in rats.2013

    • Author(s)
      S. Murase, E. Terazawa, K. Hirate, H. Yamanaka, H. Kanda, K. Noguchi, H. Ota, F. Queme, T. Taguchi, and K. Mizumura.
    • Journal Title

      Journal of Physiology

      Volume: 591 Issue: 12 Pages: 3035-3048

    • DOI

      10.1113/jphysiol.2012.249235

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of p38 MAPK through transient receptor potential A1 in a rat model of gastric distension-induced visceral pain.2013

    • Author(s)
      Kondo T, Sakurai J, Miwa H, Noguchi K.
    • Journal Title

      Neuroreport

      Volume: 24 Issue: 2 Pages: 68-72

    • DOI

      10.1097/wnr.0b013e32835c7df2

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] COX-1-dependent prostaglandin D2 in microglia contributes to neuropathic pain via DP2 receptor in spinal neurons.2013

    • Author(s)
      Kanda H, Kobayashi K, Yamanaka H, Noguchi K.
    • Journal Title

      Glia

      Volume: 61 Issue: 6 Pages: 943-956

    • DOI

      10.1002/glia.22487

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulation of TRP channels by resveratrol and other stilbenoids.2013

    • Author(s)
      Yu L, Wang S, Kogure Y, Yamamoto S, Noguchi K, Dai Y.
    • Journal Title

      Mol Pain.

      Volume: Vol.9 Pages: 3-13

    • DOI

      10.1186/1744-8069-9-3

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 神経障害性疼痛の分子メカニズム2015

    • Author(s)
      野口 光一
    • Organizer
      第68回日本自律神経学会総会
    • Place of Presentation
      ウィンクあいち(愛知県名古屋市)
    • Year and Date
      2015-10-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 神経障害性疼痛の分子メカニズム2015

    • Author(s)
      野口 光一
    • Organizer
      第44回脊椎外科を学ぶ会
    • Place of Presentation
      ツイン21МIDタワー(大阪府大阪市)
    • Year and Date
      2015-09-12
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 痛みの分子メカニズムとIASP2015

    • Author(s)
      野口 光一
    • Organizer
      日本ペインクリニック学会第49回大会
    • Place of Presentation
      グランフロント大阪(大阪府大阪市)
    • Year and Date
      2015-07-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 末梢神経損傷後の脊髄におけるPGE2合成酵素とEP受容体の発現変化2015

    • Author(s)
      神田 浩里, 小林 希実子, 山中 博樹, 大久保 正道, 野口 光一
    • Organizer
      第37回日本疼痛学会
    • Place of Presentation
      市民会館崇城大学ホール(熊本県熊本市)
    • Year and Date
      2015-07-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] Glial TNF alpha induces COX-2 expression and PGI2 synthesis in the spinal endothelial cells in neuropathic pain2014

    • Author(s)
      K.Kanda, Kobayashi K, Yamanaka H, Noguchi K.
    • Organizer
      15th World Congress on Pain
    • Place of Presentation
      Buenos Aires, Argentine
    • Year and Date
      2014-10-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] FILIPとシャペロン分子によるシナプス形態調節2014

    • Author(s)
      八木秀司, 佐藤 真, 野口光一.
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脊髄損傷モデルにおけるカルシウムチャネルα2δ-1サブユニットの発現2014

    • Author(s)
      楠山一樹, 橘 俊哉, 山中博樹, 吉矢晋一, 野口光一.
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 末梢神経損傷により誘導される脊髄Cox2/PGIS発言へのTNF alpha の関与2014

    • Author(s)
      小林希実子, 神田浩里, 山中博樹, 野口光一.
    • Organizer
      第36回日本疼痛学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-06-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 神経障害性疼痛の最近の知見を考察する2014

    • Author(s)
      野口光一.
    • Organizer
      第36回日本疼痛学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-06-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 痛みの分子メカニズム2014

    • Author(s)
      野口光一.
    • Organizer
      第24回中国・四国ペインクリニック学会
    • Place of Presentation
      高松
    • Year and Date
      2014-05-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Molecular Mechanism of Pain.2013

    • Author(s)
      Noguchi K.
    • Organizer
      The International Society for the Study of the Lumbar Spine Annual Meeting
    • Place of Presentation
      Arizona, U.S.A
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Leukotriene enhances NMDA induced inward currents in dorsal horn neurons of rat spinal cord after peripheral nerve injury.2013

    • Author(s)
      Kiyoyuki Y, Yamanaka H, Kobayashi K, Okubo M, Noguchi K, Taniguchi W, Nishio N, Nakatsuka T.
    • Organizer
      The 43nd Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      San Diego, U.S.A
    • Related Report
      2013 Annual Research Report
  • [Presentation] Expression of colony-stimulateing factors and their receptors in dorsal root ganglion and spinal cord after peripheral nerve injury.2013

    • Author(s)
      Okubo M, Yamanaka H, Kobayashi K, Kanda H, Dai Y, Noguchi K.
    • Organizer
      The 43nd Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      San Diego, U.S.A
    • Related Report
      2013 Annual Research Report
  • [Presentation] 痛みの分子メカニズムと臨床病態.2013

    • Author(s)
      野口光一
    • Organizer
      第6回日本運動器疼痛学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 痛みの分子メカニズム2013

    • Author(s)
      野口光一
    • Organizer
      第10回神経因性疼痛研究会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 侵害受容系の変化と神経障害性疼痛のメカニズム.2013

    • Author(s)
      野口光一
    • Organizer
      第42回日本脊椎脊髄病学会
    • Place of Presentation
      宜野湾
    • Related Report
      2013 Annual Research Report
    • Invited

URL: 

Published: 2013-05-21   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi